InnoSense LLC (ISL) submits this revised application with the intent of developing a cost-effective and highly sensitive polymer nanowire-based electronic biosensor (PNEBD) for the early screening of Alzheimer's disease (AD). This device is expected to have potentially significant implications in the early treatment and possible delay of debilitating symptoms associated with this disease. The Phase I project is focused on the development and verification of a high-throughput device based on silicon photolithography processes and template-free electrodeposition of functionalized conductive polymers between narrow-gap electrode junctions. Six tasks have been proposed to establish the Phase I feasibility of detecting amyloid-[unreadable] derived diffusible ligand (ADDL) antigen, a biomarker for AD, using amyloid-[unreadable] (A[unreadable]) oligomer specific antibody to ADDLs. Current evidence strongly suggests a central role for amyloid-[unreadable] (A[unreadable]) in the pathogenesis of AD. At the present time there is no definite clinical diagnosis for AD other than autopsy. It has been demonstrated that ADDLs are present at significantly elevated levels in the autopsied brain samples of humans with AD. This association of ADDLs with AD suggests that the PNEBD device could provide a definitive molecular basis for the laboratory diagnosis of AD. For ensuring success, a highly skilled research team, including an expert on AD, has been assembled to execute the project. Development of ultrasensitive detection methods for early screening of Alzheimer's disease (AD) is an important issue in clinical disease diagnosis and mechanistic understanding of Alzheimer's disease (AD). AD is a progressive neurodegenerative disease for which there is neither a cure nor an early diagnostic device. It is the leading cause of dementia in people over age 65 affecting over four million Americans. Despite its utmost importance, no ultrasensitive technologies have been developed for clinical lab diagnostic of AD. InnoSense LLC aims to fill this void by developing a cost-effective and highly-sensitive polymer nanowire-based electronic biosensor device (PNEBD). This device will utilize electrochemically grown polymer nanowires at micro- to nanoscale patterned electrode junctions for detecting amyloid-[unreadable] derived diffusible ligands (ADDLs). ADDL has been established as a biomarker for AD. The purpose of using an electrochemical method is to grow template-free, low-cost and high quality polymer nanowires on to the electrode junctions. This direct, one-step fabrication technique is scalable. This project will advance our knowledge on the detection of Alzheimer's disease.